Biomedical subjects

D F Jarrard

Publications and source records attributed to D F Jarrard.

23 records · Page 2Linked to original sources

PubMed1995

Prostate cancer staging after radiation utilizing laparoscopic pelvic lymphadenectomy.

OBJECTIVES: This report assesses the feasibility of laparoscopic pelvic lymphadenectomy in irradiated patients with prostate cancer being considered for salvage therapy. METHODS: Six men, each with a prior history of external beam radiation therapy, and prostate-specific antigen or clinical failure, were selected as potential candidates for salvage therapy. Utilizing a standard diamond pattern trocar conformation, laparoscopy was performed to evaluate pelvic lymph node status. RESULTS: The procedure was successfully completed in all patients with a mean operating room time of 154 minutes. Blood loss averaged 55 cc. Serious intraoperative or postoperative complications were not encountered in the follow-up of 6 months. Metastatic disease was demonstrated in 1 patient. CONCLUSIONS: Laparoscopic pelvic lymph node dissection is technically feasible in patients who have received irradiation, and appears to confer no additional morbidity over standard laparoscopic lymphadenectomy.

Aged↗

PubMed1995

Urokinase plasminogen activator is necessary but not sufficient for prostate cancer cell invasion.

The expression and function of urokinase plasminogen activator (uPA), an extracellular protease, were examined in four established prostate cancer lines, and one uPA-transfected cell line. The cell lines exhibited variable efficiency in uPA transcription, translation and specific proteolytic activity. A statistically significant inhibition of Boyden chamber invasion by anti-uPA monoclonal antibodies was demonstrated in cell lines TSU-PR1 and PC3. This inhibition suggests a direct role for uPA in the invasion of prostate cancer. However, variable processing of uPA mRNA, protein and proteolytic activity make prediction of in vitro invasion of prostate cancer difficult. Stable transfection experiments suggest that the proteolytic cascade generated by a cell is multiform and solitary alterations in uPA may not modify the proteolytic capability for invasion.

Animals↗

PubMed1995

Regional loss of imprinting of the insulin-like growth factor II gene occurs in human prostate tissues.

In most tissues, the insulin-like growth factor II gene (IGF-II) demonstrates imprinting, being expressed exclusively from the paternal allele. Recently, a loss of IGF-II imprinting (i.e., biallelic expression) has been found in sporadic Wilm's tumors and lung carcinomas, and this molecular event may contribute to the pathogenesis of these tumors. Here, we report that in prostates removed at radical surgery for localized adenocarcinoma, both the cancer and the associated normal peripheral zone tissue have a pronounced biallelic expression of the IGF-II gene. However, this pattern of gene expression is uncommon in periurethral samples of benign prostatic hyperplasia (BPH) from the same specimens. We analyzed the status of genomic imprinting at the IGF-II locus in prostate specimens removed for carcinoma using an ApaI polymorphism in the 3' untranslated exon of the IGF-II gene. First-strand cDNA synthesis and subsequent PCR amplification were performed on 13 of 35 radical prostatectomy specimens found to be informative for analysis of allele-specific expression. Biallelic expression for IGF-II RNA was demonstrated in 10 (83%) of 12 tumor samples and 8 (73%) of 11 matched peripheral zone prostate samples but in only 2 (18%) of 11 BPH samples. RNA transcripts were readily demonstrated by Northern blot analysis, and differences in expression were not noted among normal, BPH, and tumor prostate tissues. In situ hybridization revealed production of IGF-II by both the epithelium and stroma. The finding of a frequent biallelic expression of IGF-II in peripheral prostate specimens suggests a regional pattern of IGF-II gene regulation exists in prostate tissue. We hypothesize that this tissue-specific pattern of gene expression may participate in the marked predilection of peripheral prostatic tissue for the development of carcinogenesis.

Aged↗

PubMed1994

Effect of epidermal growth factor on prostate cancer cell line PC3 growth and invasion.

Elevated levels of epidermal growth factor (EGF) and epidermal growth factor receptor (EGF-R) have been demonstrated in prostate cancer cell lines and clinical specimens suggesting a role for polypeptide growth factors in prostate tumor cell growth and invasion. To more clearly define the role of EGF in prostate cancer invasion, we undertook a series of studies utilizing the PC3 prostate cancer cell line, an aggressive, hormone-independent cell line derived from a metastatic lesion. No statistical differences were noted in the growth of PC3 cells under serum-free conditions when EGF (10(-10) M-10(-8) M) or monoclonal anti-EGF-R antibody (10(-11) M-10(-8) M) were added. Utilizing the Boyden chamber microinvasion assay, EGF supplemented cells demonstrated a statistically significant augmentation in invasion (P < 0.05) when compared to control cells at each time point in the study. With increasing length of exposure to EGF, the number of concentrations that produced significant invasion increased: day 1 (10(-8) M), day 3 (10(-8), 10(-9) M), and day 5 (10(-7), 10(-8), 10(-10) M). Northern blot analysis of EGF supplemented cells revealed an increase in expression of urokinase plasminogen activator (uPA) RNA, a serine protease involved in the regulation of pericellular proteolysis and membrane degradation. Protein analysis confirmed these findings. Statistically significant inhibition of invasion by anti-uPA antibodies was demonstrated for EGF-stimulated and PC3 control cells. Our results demonstrate that certain concentrations of EGF augment invasion in the PC3 cell line. This enhancement of invasion occurs in part by an overproduction of uPA, an extracellular protease. These findings suggest that the autocrine production of EGF may potentiate tumor cell invasion.

Antibodies, Monoclonal↗

PubMed1993

Treatment of cyclophosphamide-induced hemorrhagic cystitis with intravesical carboprost tromethamine.

We review our experience with 18 consecutive patients who received intravesical carboprost tromethamine, an F2-alpha prostaglandin, for severe hemorrhagic cystitis following cyclophosphamide chemotherapy. Of the patients 16 were given cyclophosphamide for conditioning before bone marrow transplantation and 2 received the drug as cytotoxic therapy alone (dose range 3.6 to 15.8 gm.). All patients had severe gross hematuria that was refractory to forced diuresis and to continuous saline bladder irrigation. The intravesical prostaglandin therapy was initiated only after significant transfusion requirements (greater than 1 unit packed red blood cells per day) and/or numerous catheter manipulations for relief of clot retention. Eligible patients underwent complete clot evacuation followed by intravesical instillation of 0.4 to 1.0 mg.% carboprost tromethamine for 2 hours 4 times per day, alternating with continuous saline bladder irrigation for 2 hours. Six patients attempted an alternate protocol of 0.8 to 1.0 mg.% carboprost tromethamine given by continuous saline bladder irrigation. Complete resolution of gross hematuria occurred in 9 patients (50%). Eight patients had a partial response, with decreased transfusion requirements noted. However, complete resolution ultimately required an alternative therapy (for example formalin or urinary diversion). One patient (6%) failed to respond and required formalin therapy on day 4 of carboprost tromethamine therapy. Decreased red blood cell transfusion requirements were noted during and after therapy when compared to pretreatment values. No changes in renal or bladder function were noted during the mean followup of 17 weeks (range 1 to 64 weeks). There were 3 cases of recurrent hematuria. Side effects were limited to bladder spasm in 14 of the 18 patients (78%), with no systemic complications. The results suggest that carboprost tromethamine is a useful bedside therapy for hemorrhagic cystitis due to cyclophosphamide, and treatment appears to have minimal toxicity.

Administration, Intravesical↗